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Membrane-proximal epitope facilitates efficient T cell synapse formation by anti-FcRH5/CD3 and is a requirement for myeloma cell killing
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(2017) Membrane-proximal epitope facilitates efficient T cell synapse formation by anti-FcRH5/CD3 and is a requirement for myeloma cell killing. Cancer Cell, 31 (3). pp. 383-395. doi:10.1016/j.ccell.2017.02.001 ISSN 1535-6108.
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WRAP-membrane-proximal-epitope-facilitates-efficient-t-cell-synapse-formation-James.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (4Mb) | Preview |
Official URL: http://dx.doi.org/10.1016/j.ccell.2017.02.001
Abstract
The anti-FcRH5/CD3 T cell-dependent bispecific antibody (TDB) targets the B cell lineage marker FcRH5 expressed in multiple myeloma (MM) tumor cells. We demonstrate that TDBs trigger T cell receptor activation by inducing target clustering and exclusion of CD45 phosphatase from the synapse. The dimensions of the target molecule play a key role in the efficiency of the synapse formation. The anti-FcRH5/CD3 TDB kills human plasma cells and patient-derived myeloma cells at picomolar concentrations and results in complete depletion of B cells and bone marrow plasma cells in cynomolgus monkeys. These data demonstrate the potential for the anti-FcRH5/CD3 TDB, alone or in combination with inhibition of PD-1/PD-L1 signaling, in the treatment of MM and other B cell malignancies.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QR Microbiology > QR180 Immunology | ||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Library of Congress Subject Headings (LCSH): | Multiple myeloma -- Treatment, Bispecific antibodies, Antigenic determinants, Immune response -- Molecular aspects | ||||||||||||
| Journal or Publication Title: | Cancer Cell | ||||||||||||
| Publisher: | Elsevier | ||||||||||||
| ISSN: | 1535-6108 | ||||||||||||
| Official Date: | 13 March 2017 | ||||||||||||
| Dates: |
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| Volume: | 31 | ||||||||||||
| Number: | 3 | ||||||||||||
| Page Range: | pp. 383-395 | ||||||||||||
| DOI: | 10.1016/j.ccell.2017.02.001 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
| Date of first compliant deposit: | 26 October 2018 | ||||||||||||
| Date of first compliant Open Access: | 29 October 2018 | ||||||||||||
| RIOXX Funder/Project Grant: |
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